Association of the Cholesterol, High-Density Lipoprotein, and Glucose Index with Mortality in Sepsis Patients: Two Cohort Studies Analysis

Background Sepsis is often complicated by insulin resistance and dyslipidemia. The Cholesterol, High-Density lipoprotein, and Glucose (CHG) index is a novel marker for insulin resistance, but its prognostic role in sepsis is unclear. Methods This retrospective cohort study was conducted using the MIMIC-IV database as the derivation cohort ( n = 1325) and the eICU database as an independent external validation cohort ( n = 953). The CHG index was calculated as Ln [total cholesterol × fasting glucose / (2 × high-density lipoprotein)]. Associations between CHG tertiles (MIMIC-IV: ≤5.2, >5.2-5.6, >5.6; eICU: ≤5.3, >5.3-5.9, >5.9) and 28-day/180-day all-cause mortality were assessed using restricted cubic spline regression, Kaplan-Meier analysis, and multivariable Cox models. Results The study comprised two cohorts: the MIMIC-IV cohort ( n = 1,325, mean age 67.0 years) with 28-day and 180-day mortality rates of 24.5% and 33.4%, respectively; and the eICU validation cohort ( n = 953) with a 28-day mortality rate of 14.4%. A linear positive association was found between CHG levels and mortality risk (P for nonlinearity >0.05). Each unit increase in CHG was associated with a 46% higher 28-day mortality risk in MIMIC-IV (HR = 1.46, 95% CI: 1.18-1.81) and a 41% higher risk in eICU (HR = 1.41, 95% CI: 1.11-1.79). After full adjustment, the highest CHG tertile independently predicted increased 28-day mortality (MIMIC-IV: HR = 1.52, 95% CI: 1.13-2.03; eICU: HR = 1.97, 95% CI: 1.25-3.11) and 180-day mortality in MIMIC-IV (HR = 1.38, 95% CI: 1.08-1.75). The predictive performance was comparable to the triglyceride-glucose index. Conclusion The CHG index is an independent prognostic marker for short- and long-term all-cause mortality in sepsis patients, exhibiting a linear positive association with risk. Monitoring the CHG index may help identify high-risk patients in the ICU.